What are the 3 types of rodenticides?
- anticoagulant rodenticide: hydrocoumarins, indanediones
- neurotoxin rodenticide: bromethalin
- hypercalcemia (vit D3) rodenticide: cholicalciferol
What are the 2 most important factors to determine when dealing with rodenticide toxicity?
- what type of rodenticide was ingested
- when was the first possible exposure
What is the mechanism of toxicity of anticoagulant rodenticides?
blocks vitamin K reductase, causing cavitary bleeding
Describe the toxicokinetics of anticoagulant rodenticides.
- readily absorbed from GI tract
- peak blood level in 1-12 hours
- undergoes enterohepatic recycling
What are clinical signs of anticoagulant rodenticide toxicity? (3)
- clinical hemorrhage 2-3 days following ingestion
- cavitary bleeding most common
- hemorrhagic shock
What is the earliest test to determine if a patient has consumed a toxic dose of anticoagulant rodenticide?
PT (which tests the extrinsic coagulation pathway, factor VII, which has the shortest half life)- will be prolonged PT at 48 hour mark if a toxic dose was consumed
How do you identify acute anticoagulant rodenticide toxicity?
alteration in coagulation times and clinical signs will not yet be present b/c carboxylates vit K factors will still be present in circulation
What is the treatment for acute ingestion of anticoagulant rodenticide?
- decontamination- repeated activated charcoal for 24 hours
- if PT is prolonged at 48 hour mark without clinical bleeding--> oral vit K supplementation for 30 days (recheck PT 48 hours after discontinuing vit K)
- WITH clinical bleeding--> fresh frozen plasma, frozen plasma, cryosupernatant, whole blood, packed RBCs
What are the goals of treating the bleeding patient after anticoagulant rodenticide toxicity? (3)
- replacement of active vit K dependent clotting factors
- replace exogenous vit K
- replace RBCs if bleeding severely
Describe the properties of fresh frozen plasma, frozen plasma, cryosupernatant, whole blood, and packed RBCs.
- FFP: contains all clotting factors
- frozen plasma: contains factors II, VII, IX, and X
- cryosupernatant: contains factors II, VII, IX, and X
- whole blood: contains RBCs, all clotting factors, and platelets
- packed RBCs: only for red cell replacement
What is the mechanism of toxicity with neurotoxic rodenticide?
inhibits oxidative phosphorylation--> decreases ATP production in the CNS--> malfunction of ATP-dependent ion pump--> influx of sodium and fluid--> cerebral edema
Describe the toxicokinetics of neurotoxic rodenticide.
- enterohepatic recycling
- very long half life/ prolonged effects
What are clinical signs of neurotoxic rodenticide toxicity with acute lethal ingestion? (7)
- [within 2-24hrs]
- CNS stimulation or depression
- abnormal behavior
- focal or generalized motor seizures
- CNS abnormalities
- hind climb paralysis, ataxia, tremors
What are clinical signs of neurotoxic rodenticide toxicity with chronic low dose exposure? (8)
- loss of proprioception and deep pain
- UMN bladder
- mild to severe CNS depression
- focal or generalized motor seizures
- abnormal body postures (schiff-sherrington, decerebrate)
What is the acute toxic dose of neurotoxic rodenticide?
What is the treatment for neurotoxic rodenticide ingestion? (5)
- emesis (if exposed within the last 2-4 hours)
- decontamination (repeated activated charcoal for 24-48 hours)
- mannitol (decrease cerebral edema)
- anticonvulsant therapy
- methocarbamol for tremors
What is the mechanism of toxicity for hypercalcemic rodenticide?
high dose of cholecalciferol results in increased Ca absorption, increased urinary Ca reabsorption and increased bone mineralization--> severe hypercalcemia
Describe the toxicokinetics of hypercalcemic rodenticides.
- enterohepatic recycling
- terminal half life is weeks to months due to high fat solubility
- hypercalcemia can persist for weeks
What are clinical signs of hypercalcemic rodenticide toxicity? (7)
- [usually 36hr post ingestion]
- depression/ weakness
- GI upset
- acute renal failure
- cardiac arrhythmias
What is the treatment of hypercalcemic rodenticide toxicity?
- decontamination (repeated activated charcoal for 24 hours)
- reduction of hypercalcemia with fluid therapy, furosemide, +/- calcitonin, bisphosphonates (decreases osteoclastic behavior), steroids (reduce GI absorption of Ca), phosphorous binders
What is the mechanism of toxicity of pyrethrins/pyrethroids?
reversible neurotoxin that alters the voltage sensitive sodium channel, leading to disruption of their function
Describe the toxicokinetics of pyrethrins/ pyrethroids.
- fat soluble
- toxicity enhanced by carriers (alcohols, solvents)
- cats are more sensitive
What are the clinical signs of pyrethrin/ pyrethroid toxicity? (12)
- immune-mediated hypersensitivity- dermal manifestation
- neurotoxicity- muscle tremors, ataxia, seizures, death
- topical and oral stimulation- hypersalivation, paw flicking, ear twitching, hyperesthia, decreased activity, vomiting, diarrhea
What is the treatment for pyrethrin/ pyrethroid toxicity? (5)
- oral exposure- decontaminate
- allergic skin reaction- diphenhydramine
- neurologic reaction- muscle tremors treated with methocarbamol, seizures treated with anticonvulsants
- aggressive supportive care
What is the mechanism of toxicity of carbon monoxide?
- CO binds hemoglobin to create carboxyhemoglobin, blocks binding of oxygen--> cellular hypoxemia
- direct cytotoxicity due to altered cellular respiration--> free radical formation--> cell death
What are clinical signs of carbon monoxide poisoning?
- nausea/ vomiting
- red MMs
How is CO poisoning diagnosed? (2)
- CO-oximetry: confirms CO toxicity by measuring the amount of hemoglobin, oxygen saturation, and percentage of CO-Hgb
- arterial blood sample: PaO2 will represent dissolved oxygen in blood d/t oxyhemoglobin curve being shifted to the left; monitor response to therapy this way
- [pulse ox: not accurate, CO-Hgb absorbs the same wavelength as O-Hgb]
What is the treatment for CO toxicity? (2)
- oxygen supplementation
- supportive care
What is the mechanism of toxicity with ethylene glycol?
- EG itself is not toxic
- its metabolites from the liver result in clinical disease by forming oxalates, which are nephrotoxic and result in mineralization of renal tissue
What are clinical signs of ethylene glycol toxicity, separated by timeframe?
- 30 min: nausea and vomiting, CNS depression, ataxia, LMN signs in limbs, muscle fasiculations, PU/PD
- 24-72 hours: signs of AKI- depression, anorexia, vomiting, seizures, pytalism, oral ulceration, and coma
- 72-96 hours: anuria, cats may have swollen painful kidneys
How is ethylene glycol toxicity diagnosed? (7)
- elevated osmolal gap (1 hour following ingestion and remain elevated for 18 hours) [2(Na+K) + (BUN/2.8) + (glucose/18)]
- high anion gap (within 3 hours of ingestion) [(Na+K)- (Cl+HCO3)]
- urinalysis: calcium oxalate crystals (within 3-6 hours), isosthenuria
- also EG test kits available
- biochem: azotemia, hyperPh, hyperK
- abdominal US: halo sign/ hyperechoic renal cortex
What is the treatment of ethylene glycol toxicity? (3)
- 4-MP or fomepizole (alcohol dehydrogenase inhibitor, block conversion of EG to toxic metabolites)
- ethanol 20% (competitive substrate for alcohol dehydrogenase, bloc conversion to toxic metabolites)
- hemodialysis (remove EG and toxic metabolites)
- [note: decontamination NOT helpful]